Dr. David Aguilar is a non-invasive cardiologist strongly committed to a career in clinical research. He completed his internal medicine residency and cardiology fellowship at the Brigham and Women's Hospital, Harvard Medical School and is currently an Assistant Professor of Medicine at Baylor College of Medicine (BCM). This Mentored Career Development Award (K01) will develop Dr. Aguilar's career through several mechanisms, including weekly mentoring meetings, the Clinical Scientist Training Program, and didactic coursework at the University of Texas School of Public Health and BCM. As part of the award, Dr. Aguilar will address the importance of aortic and left ventricular (LV) diastolic stiffness in diabetic patients with heart failure (HF) and normal ejection fraction (EF) and will test the effects of a treatment strategy with a glucagon-like peptide-1 (GLP-1) receptor activator (exenatide) on aortic and LV diastolic stiffness. Diabetes is commonly seen in patients with HF and normal EF and is associated with increased morbidity and mortality. The mechanisms contributing to these adverse outcomes in diabetic patients are poorly understood and represent a barrier to improving outcomes. We hypothesize that, in patients with HF and normal EF, LV diastolic stiffness will be greater in diabetic patients than in non-diabetic patients and that this increased LV diastolic stiffness will correlate with increased aortic stiffness. We also hypothesize that this increased LV diastolic stiffness will correlate with serum biomarkers of increased myocardial collagen accumulation. The importance of advanced glycation end products (AGEs) in this process will be examined by also testing the hypothesis that increased aortic stiffness and LV diastolic stiffness are directly correlated with increased serum levels of AGEs. Finally, we hypothesize that treatment of type 2 diabetes with exenatide for 12 weeks in individuals with HF and normal EF will be associated with improvement in aortic and LV diastolic stiffness and in serum biomarkers of abnormal myocardial collagen accumulation. Given the increasing prevalence of diabetes and the burden of disease attributed to both diabetes and HF with normal EF, this work has significant public health implications. Dr. Aguilar will study mechanisms contributing to the adverse outcomes in diabetic individuals with HF and normal EF and will test a diabetes-specific treatment strategy in hopes of improving outcomes in this high-risk group of patients.